Radiotherapy is one of the most common cancer treatments. It damages the DNA, causing cancer cells to stop growing and die if the damage is left unrepaired. Unfortunately, some cancers are resistant to radiotherapy and the treatment also damages the DNA in healthy cells, thus limiting the amount of radiation that can be used with respect to normal tissue damage.
In collaboration with the Swedish company Kancera AB, researchers at Karolinska Institutet have discovered a new mechanism that cancer cells use to repair DNA damage. In the current study, the researchers discovered that cancer cells use a protein called PFKFB3 to repair the DNA damage that occurs in radiation therapy. They found that the protein locates to sites of DNA damage in the cell nucleus where the protein regulates the cancer cell's ability to repair its DNA and thus survive.
The research groups at Kancera AB and Karolinska Institutet have now developed a new drug candidate which blocks the protein and its ability to repair DNA damage. They demonstrated that cancer cells treated with the drug do not survive upon radiotherapy in laboratory experiments.
“It is known that the levels of PFKFB3 is much higher in cancer cells than in healthy cells. However, the discovery that PFKFB3 regulates DNA repair upon radiotherapy is new and very exciting,” says Nina Gustafsson, Assistant Professor and Team Leader in Translational Medicine at the Department of Oncology-Pathology, Karolinska Institutet, who led the study together with Professor Thomas Helleday at the same department.
Since normal, healthy cells are not dependent on PFKFB3 for proper DNA repair, the researchers hope that combination therapy with radiation or chemotherapy will be well tolerated. The goal is now to further develop the drug and lay the foundation for a new cancer treatment with less side effects than the treatments currently available.
Source: Karolinska Institutet